Synlett 2005(2): 349-351  
DOI: 10.1055/s-2004-837197
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Radical Approach for the Construction of the Tricyclic Core of Stemoamide

Nicolas Bogliotti, Peter I. Dalko, Janine Cossy*
Laboratoire de Chimie Organique associé au CNRS, ESPCI, 10 rue Vauquelin, 75231 Paris Cedex 05, France
e-Mail: Janine.Cossy@espci.fr;
Further Information

Publication History

Received 30 September 2004
Publication Date:
17 December 2004 (online)

Abstract

A rapid synthesis of (±)-9,10-bis-epi-stemoamide is presented. Three of the four contiguous stereocenters of this compound were set in a diastereoselective radical 7-exo-trig cyclization, which also allowed the construction of the tricyclic core of the molecule.

10

For general conditions of cyclization see ref. [11]

11

9,10-bis- epi -Stemoamide ( 10):
To a stirred solution of 9 (48 mg, 0.15 mmol) and AIBN (5 mg, 0.03 mmol) in degassed benzene (30 mL) at reflux, a solution of Bu3SnH (100 µL, 0.37 mmol) in benzene (3 mL) was added over 4 h via a syringe pump. The crude mixture was treated with a sat. aq solution of KF, extracted by CH2Cl2, dried over MgSO4, filtered, concentrated under reduced pressure, and purified by chromatography on silica gel (gradient: CH2Cl2 then CH2Cl2-MeOH 95:5) to afford compound 10 (6.7 mg, 0.03 mmol, 20%) as a single diastereomer. 1H NMR (300 MHz, CDCl3): δ = 1.39 (d, J = 7.2 Hz, 3 H), 1.61-2.15 (br m, 5 H), 2.23-2.62 (m, 5 H), 2.78 (ddd, J = 13.9, 10.4, 3.4 Hz, 1 H), 3.63 (dd, J = 9.0, 7.2 Hz, 1 H), 4.18 (dt, J = 13.9, 4.5 Hz, 1 H), 4.62 (ddd, J = 10.6, 7.9, 3.0 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 15.9, 24.0, 25.5, 28.9, 30.1, 39.1, 44.1, 50.9, 60.5, 80.7, 174.6, 177.9. MS (EI, 70eV): m/z (%) = 224 (12) [MH+ ], 223 (87) [M+ ], 208 (41), 180 (44), 98 (100), 97 (59).